Cannabinoids control spasticity and tremor in a multiple sclerosis model

David Baker (), Gareth Pryce, J. Ludovic Croxford, Peter Brown, Roger G. Pertwee, John W. Huffman and Lorna Layward
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David Baker: Neuroinflammation Group, Institute of Neurology, University College London
Gareth Pryce: Neuroinflammation Group, Institute of Neurology, University College London
J. Ludovic Croxford: Neuroinflammation Group, Institute of Neurology, University College London
Peter Brown: The Medical Research Council Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery
Roger G. Pertwee: University of Aberdeen
John W. Huffman: Clemson University
Lorna Layward: Multiple Sclerosis Society of Great Britain and Northern Ireland

Nature, 2000, vol. 404, issue 6773, 84-87

Abstract: Abstract Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis1. Although both these diseases are typified by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens1 Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are difficult to control. This has prompted some patients to find alternative medicines, and to perceive benefit from cannabis use2. Although this benefit has been backed up by small clinical studies, mainly with non-quantifiable outcomes3,4,5,6,7, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, Δ9-tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) quantitatively ameliorated both tremor and spasticity in diseased mice. The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis2, and provides a means of evaluating more selective cannabinoids in the future.

Date: 2000
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DOI: 10.1038/35003583

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